Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey.
Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey.
Endocr Relat Cancer. 2024 Sep 27;31(11). doi: 10.1530/ERC-24-0101. Print 2024 Nov 1.
Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAEs. The study prospectively included 43 patients with metastatic disease scheduled for anti-PD-1/L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta, and IL-17A were measured prior to ICI and during the endocrine-irAEs. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the non-irAE group (P < 0.05), whereas IL-1beta and IL-17A levels did not differ (P > 0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (P > 0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r = 0.706, P = 0.01) and negatively with baseline total testosterone level of men (r = 0.509, P = 0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction.
免疫检查点抑制剂 (ICIs) 可引发免疫相关不良反应 (irAEs)。irAEs 的出现模式、易患人群及其机制仍不确定。在这项研究中，我们旨在监测接受 ICI 治疗的患者的内分泌学方面，并研究内分泌 irAEs 发展中的潜在预测标志物。该研究前瞻性纳入了 43 例转移性疾病患者，计划接受抗 PD-1/L1 治疗。根据规定的间隔以及任何额外报告的投诉进行内分泌学随访。在接受 ICI 治疗前和内分泌 irAEs 期间测量了血清 CXCL10、IL-1beta 和 IL-17A 浓度。共有 39.5%的患者发生内分泌 irAEs，中位发病时间为 3 个月。其中，34.9%的患者发生甲状腺相关不良反应，4.6%的患者发生垂体炎。甲状腺自身抗体与甲状腺相关 irAEs 的发生率较高相关（P = 0.004）。在 irAE 组中，中位 ICI 前 CXCL10 和基线促甲状腺激素 (TSH) 水平显著较高，男性基线总睾酮水平低于非 irAE 组（P < 0.05），而 IL-1beta 和 IL-17A 水平无差异（P > 0.05）。ICI 前和不良事件期间血清 CXCL10、IL-1beta 和 IL-17A 浓度无显著差异（P > 0.05）。至少有一种甲状腺自身抗体阳性的患者中，ICI 前 CXCL10 浓度与抗 TPO 水平呈正相关（r = 0.706，P = 0.01），与男性基线总睾酮水平呈负相关（r = 0.509，P = 0.002）。我们的结果表明，较高的 ICI 前血清 CXCL10 和 TSH 水平可能对内分泌疾病的发生具有预测作用。此外，基线甲状腺抗体测量可能有助于预测甲状腺功能障碍。
